Among the fundamental goals of neuroscience is to understand the form, function, and development of the system of sensory and motor maps that are ubiquitous in higher nervous systems. The ordered arrangement of afferent projections from the thalamus to the cortex is the most thoroughly studied model system for exploring the function and development of sensory maps in mammals. This system is characterized by an array of thalamic afferents that form organized projections into cortical columns serving different stimulus variables, such as ocular dominance in visual cortex or whisker preference in somatosensory cortex. The pattern of thalamocortical projections undergoes an activity dependent elaboration and refinement that leads to the development of cortical columns with very selective stimulus response features. This process is influenced by changes in sensory experience, such as monocular visual deprivation or whisker cauterization, which leads to dramatically altered sensory maps, particularly when the deprivation is started in an early 'critical period' during development. The overall goal of the proposed experiments is to elucidate the mechanisms that mediate the development and plasticity of sensory maps in cortex. These experiments will be executed with a combination of anatomical, biochemical and electrophysiological approaches using normal and mutant or transgenic mice with specific emphasis on examining the mechanisms of whisker 'barrel' column development and plasticity in the somatosensory cortex of the rodent. A detailed explanation of these mechanisms will allow us to understand at a cellular level how molecules, neural activity and sensory experience together guide the development of brain circuitry. Ultimately, these same mechanisms are likely to be involved in the pathogenesis of behavioral disorders with a complex combination of genetic and experiential etiologies, such as Autism and Schizophrenia. This research aims to understand the cellular and molecular mechanisms responsible for how the brain wires itself up during development. Several brain disorders, including Epilepsy, Autism and Schizophrenia are thought to be caused by errors in this process, with abnormal brain function and behavior the result of miswiring that occurs in the developing brain. [unreadable] [unreadable]